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Is Hyperthermia during Epidural Anesthesia a Complication of the Anesthetic? Negishi et al.(page 218)

To explore the mechanisms of hyperthermia associated with epidural anesthesia, Negishi et al. recruited eight male volunteers to participate in four separate experiments on four study days. On each study day, an intravenous injection of 50 IU/g human recombinant interleukin (IL)-2 was administered to participants, followed by 100 IU/g of the drug 2 h later. The volunteers then were assigned randomly to one of four protocols: (1) control day without opioid or epidural anesthesia; (2) epidural analgesia using 0.2% ropivacaine alone; (3) epidural analgesia using 0.2% ropivacaine combined with 2.0 μg/ml fentanyl; or (4) intravenous fentanyl administered at a target plasma concentration of 2.5 ng/ml. Researchers allowed 2 weeks between the fentanyl day and the combined ropivacaine–fentanyl day to minimize drug tolerance.

Febrile responses to pyrogen were measured up to 8 h in each volunteer. Additional measurements included plasma concentrations of IL-6, IL-8, and tumor necrosis factor α, as well as blood pressure, heart rate, and arterial oxygen saturation. Core temperatures of the volunteers peaked at 38.7 ± 0.6°C on the control day, at 38.7 ± 0.7°C during epidural ropivacaine, and at 38.7 ± 0.9°C with combined epidural fentanyl and ropivacaine, but only increased to 38.1 ± 0.7°C on the day intravenous fentanyl was administered to the volunteers. The area under the temperature–time curve for fentanyl was roughly 50% less than for the other groups. Therefore, fentanyl significantly reduced febrile responses to pyrogen, whereas neither epidural ropivacaine nor epidural fentanyl–ropivacaine inhibited manifestation of fever as compared with controls.

From these results, the researchers concluded that hyperthermia during epidural analgesia is not caused by the anesthetic but should be considered as evidence of underlying infection or inflammation and should be treated seriously. In addition, because opioids tend to attenuate fever, the researchers recommended that threshold temperatures triggering investigations for infection be reduced approximately 0.5°C in patients to whom opioid analgesia is administered.